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The Thioredoxin System Powers ArsM-Mediated Arsenite Methylation in Hymenobacter edaphi
Xue-Ting Li1, Jie Shen1, David Bickel2,3
1Jiangsu Key Laboratory for Organic Waste Utilization, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095, China.
Abstract:
Arsenic biomethylation plays a critical role in modulating environmental arsenic toxicity yet remains understudied in the phylum Bacteroidetes. Here, we characterize HeArsM, a methyltransferase from the soil bacterium Hymenobacter edaphi, which effectively methylates arsenite [As(III)] into various species. We demonstrated that this activity is primarily supported by the thioredoxin (Trx)-thioredoxin reductase (TR)-NADPH system, which is significantly more effective than alternative reductants such as glutathione/glutaredoxin (GSH/Grx), cysteine, or tris(2-carboxyethyl)phosphine (TCEP). Site-directed mutagenesis identified Cys23, Cys48, and Cys143 as essential for catalysis, with Cys143 uniquely required for monomethylarsenite [MMAs(III)] methylation. Structural modeling using AlphaFold and energy minimization supports a thiol-disulfide exchange mechanism as the basis for arsenic methylation. These findings provide mechanistic insight into arsenic detoxification in Bacteroidetes and highlight H. edaphi as a model for understanding microbial arsenic cycling in terrestrial environments.
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